Ciprofol is a new intravenous anesthetic agent similar to propofol that has the pharmacodynamic characteristics of a rapid rate of onset and recovery in pre-clinical experiments. The aims of the present clinical trials were to compare the efficacy and safety of ciprofol emulsion for sedation or general anesthesia during colonoscopy and to define optimal doses for a subsequent phase III clinical trial. A phase IIa multi-center, open-label, non-randomized, positive control, dose-escalating study was performed to determine a recommended phase IIb dose (RP2D) of ciprofol to induce sedation or anesthesia in patients undergoing colonoscopy. Phase IIb was also a multi-center clinical trial, but the patients were randomized into 3 groups at a ratio of 1:1:1. It was a double-blinded, propofol controlled study that administered ciprofol 0.4 mg/kg (n = 31) and 0.5 mg/kg (n = 32) or propofol at 2.0 mg/kg (n = 31), with the aim of establishing the optimal dose of ciprofol. The primary endpoint was the colonoscopy success rate. Secondary endpoints were the duration of colonoscope insertion, recovery time, number of top-up doses needed, and the total dose of ciprofol or propofol required to maintain adequate sedation or anesthesia. In addition, we evaluated the satisfaction of sedation/anesthesia from the endoscopists, anesthetists and patients' points of view. Safety was assessed according to the incidence of AEs including serious AEs and drug related AEs and the assessment of vital signs, a 12-lead ECG and laboratory tests. In the phase IIa trial, the colonoscopy success rates in the 0.2-0.5 mg/kg ciprofol and propofol 2.0 mg/kg groups were 100% and all doses were safe and well tolerated. Ciprofol doses of 0.4 mg/kg and 0.5 mg/kg are recommended for subsequent IIb phases. In the phase IIb trial, a 100% success rate was reconfirmed in all the dosage groups. The mean time of colonoscope insertion in the ciprofol 0.4 mg/kg, ciprofol 0.5 mg/kg and propofol 2.0 mg/kg groups were 1.9, 1.5 and 1.5 min, the mean recovery times from colonoscope withdrawal were 6.1, 5.1, and 4.3 min, and the times to discharge were 11.8, 11.2 and 10.6 min, respectively. The satisfaction ratings of anesthetists in the ciprofol 0.5 mg/kg group (9.5 ± 0.8) were higher than in the ciprofol 0.4 mg/kg (9.2 ± 1.0) and propofol 2.0 mg/kg (9.2 ± 0.9) groups. The incidence of sedation and anesthesia-related AEs was highest in the propofol 2.0 mg/kg group (25.8%), followed by the ciprofol 0.5 mg/kg group (21.9%), and was least in the ciprofol 0.4 mg/kg group (16.1%) (P = 0.750). Ciprofol was safe and well tolerated at doses ranging from 0.1 mg/kg to 0.5 mg/kg. Ciprofol 0.4-0.5 mg/kg induced equivalent sedation/anesthesia and had a similar safety profile to propofol 2.0 mg/kg during colonoscopy without producing serious AEs.

Ciprofol is a propofol analogue with improved pharmacokinetic properties. A multi‐centre, non‐inferiority trial was conducted to compare the deep sedation properties of ciprofol and propofol with a non‐inferiority margin of 8% in patients undergoing gastroscopy and colonoscopy. In total, 289 patients were randomly allocated for surgery (259 colonoscopy and 30 gastroscopy) at a 1:1 ratio to be given intravenous injections of ciprofol (0.4 mg/kg) or propofol (1.5 mg/kg). The primary outcome was the success rate of colonoscopy defined as colonoscopy completion with no need for an alternative sedative or >5 ciprofol or propofol top up doses within any 15‐min time period. The success rate of colonoscopy was 100% in the ciprofol group vs. 99.2% in the propofol group (mean difference 0.8%, 95% CI: −2.2% to 4.2%). Except for the gastrointestinal lesions found during the gastroscopy and colonoscopy procedures, the occurrence rates of adverse drug reactions in the ciprofol and propofol groups were 31.3% and 62.8%, respectively (P < 0.001). Pain on injection was less common in the ciprofol group (4.9% vs. 52.4%, P < 0.001). The outcomes demonstrated that ciprofol was non‐inferior to propofol with regard to successful sedation for gastroscopy or colonoscopy procedures and no obvious important adverse events occurred.

Lidocaine, as the only local anesthetic approved for intravenous administration in the clinic, can relieve neuropathic pain, hyperalgesia, and complex regional pain syndrome. Intravenous injection of lidocaine during surgery is considered as an effective strategy to control postoperative pain, but the mechanism of its analgesic effect has not been fully elucidated. This paper intends to review recent studies on the mechanism of the analgesic effect of lidocaine. To the end, we conducted an electronic search of the PubMed database. The search period was from 5 years before June 2019. Lidocaine was used as the search term. A total of 659 documents were obtained, we included 17 articles. These articles combined with the 34 articles found by hand searching made up the 51 articles that were ultimately included. We reviewed the analgesic mechanism of lidocaine in the central nervous system.

The value of goal-directed fluid therapy in neurosurgical patients, where brain swelling is a major concern, is unknown. The aim of our study was to evaluate the effect of an intraoperative goal-directed fluid restriction (GDFR) strategy on the postoperative outcome of high-risk patients undergoing brain surgery. High-risk patients undergoing brain surgery were randomly assigned to a usual care group (control group) or a GDFR group. In the GDFR group, (1) fluid maintenance was restricted to 3 ml/kg/h of a crystalloid solution and (2) colloid boluses were allowed only in case of hypotension associated with a low cardiac index and a high stroke volume variation. The primary outcome variable was ICU length of stay, and secondary outcomes were lactates at the end of surgery, postoperative complications, hospital length of stay, mortality at day 30, and costs. A total of 73 patients from the GDFR group were compared with 72 patients from the control group. Before surgery, the two groups were comparable. During surgery, the GDFR group received less colloid (1.9 ± 1.1 vs. 3.9 ± 1.6 ml/kg/h, p = 0.021) and less crystalloid (3 ± 0 vs. 5.0 ± 2.8 ml/kg/h, p < 0.001) than the control group. ICU length of stay was shorter (3 days [1–5] vs. 6 days [3–11], p = 0.001) and ICU costs were lower in the GDFR group. The total number of complications (46 vs. 99, p = 0.043) and the proportion of patients who developed one or more complications (19.2 vs. 34.7%, p = 0.034) were smaller in the GDFR group. Hospital length of stay and costs, as well as mortality at 30 day, were not significantly reduced. In high-risk patients undergoing brain surgery, intraoperative GDFR was associated with a reduction in ICU length of stay and costs, and a decrease in postoperative morbidity. Trial registration Chinese Clinical Trial Registry ChiCTR-TRC-13003583, Registered 20 Aug, 2013

Emerging evidence suggests that Toll-like receptors (TLRs) ligands pretreatment may play a vital role in the progress of myocardial ischemia/reperfusion (I/R) injury. As the ligand of TLR3, polyinosinic-polycytidylic acid (poly(I:C)), a synthetic double-stranded RNA, whether its preconditioning can exhibit a cardioprotective phenotype remains unknown. Here, we report the protective effect of poly(I:C) pretreatment in acute myocardial I/R injury by activating TLR3/PI3K/Akt signaling pathway. Poly(I:C) pretreatment leads to a significant reduction of infarct size, improvement of cardiac function, and downregulation of inflammatory cytokines and apoptotic molecules compared with controls. Subsequently, our data demonstrate that phosphorylation of TLR3 tyrosine residue and its interaction with PI3K is enhanced, and protein levels of phospho-PI3K and phospho-Akt are both increased after poly(I:C) pretreatment, while knock out of TLR3 suppresses the cardioprotection of poly(I:C) preconditioning through a decreased activation of PI3K/Akt signaling. Moreover, inhibition of p85 PI3K by the administration of LY294002 in vivo and knockdown of Akt by siRNA in vitro significantly abolish poly(I:C) preconditioning-induced cardioprotective effect. In conclusion, our results reveal that poly(I:C) preconditioning exhibits essential protection in myocardial I/R injury via its modulation of TLR3, and the downstream PI3K/Akt signaling, which may provide a potential pharmacologic target for perioperative cardioprotection.